Summary

Neurodegeneration refers to the progressive loss of neuron structure or function, which may eventually lead to cell death. Many neurodegenerative diseases, such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease and prion disease, are the results of neurodegenerative processes. Neurodegeneration can be found in many different levels of neuronal circuits in the brain, from molecules to systems. Since there is no known method to reverse the progressive degeneration of neurons, these diseases are considered incurable. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assembly (such as protein diseases) and induction of cell death. These similarities indicate that progress in the treatment of one neurodegenerative disease may also improve other diseases. This collection of entries aims to collect various medical research results related to neurodegeneration. We invite researchers to share their new results and ideas related to neurodegeneration.

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Entries
Topic Review
Inflammation in Spinal Cord Injury
Spinal cord injury (SCI) is a pathological neurological condition leading to significant motor dysfunction. SCI is most often caused by mechanical damage (also called primary damage) and the secondary damage that is caused by inflammation. The initial injury triggers successive pathophysiological cascades and activates cellular processes that contribute to secondary tissue damage. The blood–spinal cord barrier is destroyed, which promotes the infiltration of macrophages, neutrophils, and T lymphocytes into the damaged area.
  • 624
  • 23 Nov 2022
Topic Review
Nrf2/Bach1 Signaling Pathway in Parkinson’s Disease
Parkinson’s disease (PD) is the second most common neurodegenerative movement disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Although a complex interplay of multiple environmental and genetic factors has been implicated, the etiology of neuronal death in PD remains unresolved. Various mechanisms of neuronal degeneration in PD have been proposed, including oxidative stress, mitochondrial dysfunction, neuroinflammation, α-synuclein proteostasis, disruption of calcium homeostasis, and other cell death pathways. While many drugs individually targeting these pathways have shown promise in preclinical PD models, this promise has not yet translated into neuroprotective therapies in human PD. This has consequently spurred efforts to identify alternative targets with multipronged therapeutic approaches. A promising therapeutic target that could modulate multiple etiological pathways involves drug-induced activation of a coordinated genetic program regulated by the transcription factor, nuclear factor E2-related factor 2 (Nrf2). Nrf2 regulates the transcription of over 250 genes, creating a multifaceted network that integrates cellular activities by expressing cytoprotective genes, promoting the resolution of inflammation, restoring redox and protein homeostasis, stimulating energy metabolism, and facilitating repair. Researchers propose that the transcriptional repressor of BTB and CNC homology 1 (Bach1), which antagonizes Nrf2, could serve as a promising complementary target for the activation of both Nrf2-dependent and Nrf2-independent neuroprotective pathways. Here this entry present the knowledge on the Nrf2/Bach1 signaling pathway, its role in various cellular processes, and the benefits of simultaneously inhibiting Bach1 and stabilizing Nrf2 using non-electrophilic small molecules as a novel therapeutic approach for PD.
  • 481
  • 25 Nov 2022
Topic Review
Esterification of Docosahexaenoic Acid  in Brain Diseases
Docosahexaenoic acid-containing lysophosphatidylcholine (DHA-LysoPC) is presented as the main transporter of DHA from blood plasma to the brain. This is related to the major facilitator superfamily domain-containing protein 2A (Mfsd2a) symporter expression in the blood–brain barrier that recognizes the various lyso-phospholipids that have choline in their polar head. In order to stabilize the DHA moiety at the sn-2 position of LysoPC, the sn-1 position was esterified by the shortest acetyl chain, creating the structural phospholipid 1-acetyl,2-docosahexaenoyl-glycerophosphocholine (AceDoPC). This small structure modification allows the maintaining of the preferential brain uptake of DHA over non-esterified DHA. Additional properties were found for AceDoPC, such as antioxidant properties, especially due to the aspirin-like acetyl moiety, as well as the capacity to generate acetylcholine in response to the phospholipase D cleavage of the polar head. Esterification of DHA within DHA-LysoPC or AceDoPC could elicit more potent neuroprotective effects against neurological diseases.
  • 482
  • 22 Nov 2022
Topic Review
Forms of Parkinson Disease Epigenetic Aspects
Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting approximately 1% of the population over the age of 50. PD is the second most common neurodegenerative disorder, and the estimated prevalence is 94 cases per 100,000 people, or approximately 0.3 percent in the general population 40 years of age and older. The yearly incidence of new cases ranges from 8 to 18.6 per 100,000 person-years. PD is clinically characterized by uncontrollable tremors at rest, rigidity, slowness of movement and postural impairment. In addition to violations of motor function, PD is accompanied by gastrointestinal, olfactory, sleep, and cognitive pathologies and other disorders. PD is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). These neurons release dopamine (DA) from nerve endings in the striatum and control muscle tone and multiple brain functions including a broad array of behavioral processes such as mood, reward, addiction, and stress. Morphologically PD is characterized by the presence of intracellular inclusions called Lewy bodies (LB) consisting mainly of aggregated α-synuclein (αSyn) inside nerve cells including SNpc. The onset of PD is dependent on both genetic and environmental factors. The latter can alter gene expression by causing epigenetic changes, such as DNA methylation, and the post-translational modification of histones and non-coding RNAs (ncRNAs, the most studied of which are microRNAs or miRNAs). The regulation of genes responsible for monogenic forms of PD may also be involved in sporadic PD.
  • 626
  • 12 Sep 2023
Topic Review
Melatonin as a Neurotrophic Factor
Melatonin, N-acetyl-5-hydroxytryptamine, is a hormone that synchronizes the internal environment with the photoperiod. It is synthesized in the pineal gland and greatly depends on the endogenous circadian clock located in the suprachiasmatic nucleus and the retina’s exposure to different light intensities. Among its most studied functions are the regulation of the waking-sleep rhythm and body temperature. Furthermore, melatonin has pleiotropic actions, which affect, for instance, the modulation of the immune and the cardiovascular systems, as well as the neuroprotection achieved by scavenging free radicals.
  • 1.3K
  • 19 Nov 2022
Topic Review
P2Y1 Receptor as a Catalyst of Brain Neurodegeneration
Different brain disorders display distinctive etiologies and pathogenic mechanisms. However, they also share pathogenic events. One event systematically occurring in different brain disorders, both acute and chronic, is the increase of the extracellular ATP levels. Accordingly, several P2 (ATP/ADP) and P1 (adenosine) receptors, as well as the ectoenzymes involved in the extracellular catabolism of ATP, have been associated to different brain pathologies, either with a neuroprotective or neurodegenerative action. The P2Y1 receptor (P2Y1R) is one of the purinergic receptors associated to different brain diseases. It has a widespread regional, cellular, and subcellular distribution in the brain, it is capable of modulating synaptic function and neuronal activity, and it is particularly important in the control of astrocytic activity and in astrocyte–neuron communication. In diverse brain pathologies, there is growing evidence of a noxious gain-of-function of P2Y1R favoring neurodegeneration by promoting astrocyte hyperactivity, entraining Ca2+-waves, and inducing the release of glutamate by directly or indirectly recruiting microglia and/or by increasing the susceptibility of neurons to damage.
  • 469
  • 21 Nov 2022
Topic Review
Strategies for AAV-Based Therapy of Ducheen Muscular Dystrophin
Gene therapy using the adeno-associated virus (rAAV) to deliver mini/micro- dystrophin is the current promising strategy for Duchenne Muscular Dystrophy (DMD). However, the further transformation of this strategy still faces many “bottlenecks”. Most gene therapies are only suitable for infants with strong muscle cell regeneration and immature immune system, and the treatment depends heavily on the high dose of rAAV. However, high-dose rAAV inevitably causes side effects such as immune response and acute liver toxicity. Therefore, how to reduce the degree of fibrosis and excessive immune response in older patients and uncouple the dependence association between therapeutic effect and high dose rAAV are crucial steps for the transformation of rAAV-based gene therapy. 
  • 865
  • 18 Nov 2022
Topic Review
Stem-Cell-Based Therapy in Alzheimer’s Disease
Stem cells are a versatile source for cell therapy. Their use is particularly significant for the treatment of neurological disorders for which no definitive conventional medical treatment is available. Neurological disorders are of diverse etiology and pathogenesis. Alzheimer’s disease (AD) is caused by abnormal protein deposits, leading to progressive dementia.
  • 432
  • 15 Nov 2022
Topic Review
Treatment for Preterm Brain Injury
With a worldwide incidence of 15 million cases, preterm birth is a major contributor to neonatal mortality and morbidity, and concomitant social and economic burden Preterm infants are predisposed to life-long neurological disorders due to the immaturity of the brain. The risks are inversely proportional to maturity at birth. In the majority of extremely preterm infants (<28 weeks’ gestation), perinatal brain injury is associated with exposure to multiple inflammatory perinatal triggers that include antenatal infection (i.e., chorioamnionitis), hypoxia-ischemia, and various postnatal injurious triggers (i.e., oxidative stress, sepsis, mechanical ventilation, hemodynamic instability).
  • 523
  • 15 Nov 2022
Topic Review
G Protein-Coupled Receptor with the Aging-Related Mechanisms
G protein-coupled receptors (GPCRs) represent one of the most functionally diverse classes of transmembrane proteins. GPCRs and their associated signaling systems have been linked to nearly every physiological, and also pathophysiological, process. G protein-coupled receptor 19 (GPR19), is a novel orphan GPCR that likely represents an important new target for novel remedial strategies for pathological disease conditions associated with aging-related cellular and tissue damage.
  • 1.1K
  • 16 Nov 2022
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